The evolution of vertebrate tetraspanins: gene loss, retention, and massive positive selection after whole genome duplications

<p>Abstract</p> <p>Background</p> <p>The vertebrate tetraspanin family has many features which make it suitable for preserving the imprint of ancient sequence evolution and amenable for phylogenomic analysis. So we believe that an in-depth analysis of the tetraspanin evolution not only provides more complete understanding of tetraspanin biology, but offers new insights into the influence of the two rounds of whole genome duplication (2R-WGD) at the origin of vertebrates.</p> <p>Results</p> <p>A detailed phylogeny of vertebrate tetraspanins was constructed by using multiple lines of information, including sequence-based phylogenetics, key structural features, intron configuration and genomic synteny. In particular, a total of 38 modern tetraspanin ortholog lineages in bony vertebrates have been identified and subsequently classified into 17 ancestral lineages existing before 2R-WGD. Based on this phylogeny, we found that the ohnolog retention rate of tetraspanins after 2R-WGD was three times as the average (a rate similar to those of transcription factors and protein kinases). This high rate didn't increase the tetrapanin family size, but changed the family composition, possibly by displacing vertebrate-specific gene lineages with the lineages conserved across deuterostomes. We also found that the period from 2R-WGD to recent time is controlled by gene losses. Meanwhile, positive selection has been detected on 80% of the branches right after 2R-WGDs, which declines significantly on both magnitude and extensity on the following speciation branches. Notably, the loss of mammalian RDS2 is accompanied by strong positive selection on mammalian ROM1, possibly due to gene loss-induced compensatory evolution.</p> <p>Conclusions</p> <p>First, different from transcription factors and kinases, high duplicate retention rate after 2R-WGD didn't increase the tetraspanin family size but just reshaped the family composition. Second, the evolution of tetraspanins right after 2R-WGD had been impacted by a massive wave of gene loss and positive selection on coding sequences. Third, the lingering effect of 2R-WGD on tetraspanin gene loss and positive selection might last for 300-400 million years.</p

Temporal and structural patterns of hepatitis B virus integrations in hepatocellular carcinoma

Chronic infection of hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC). Notably, 90% of HBV-positive HCC cases exhibit detectable HBV integrations, hinting at the potential early entanglement of these viral integrations in tumorigenesis and their subsequent oncogenic implications. Nevertheless, the precise chronology of integration events during HCC tumorigenesis, alongside their sequential structural patterns, has remained elusive thus far. In this study, we applied whole-genome sequencing to multiple biopsies extracted from six HBV-positive HCC cases. Through this approach, we identified point mutations and viral integrations, offering a blueprint for the intricate tumor phylogeny of these samples. The emergent narrative paints a rich tapestry of diverse evolutionary trajectories characterizing the analyzed tumors. We uncovered oncogenic integration events in some samples that appear to happen before and during the initiation stage of tumor development based on their locations in reconstituted trajectories. Furthermore, we conducted additional long-read sequencing of selected samples and unveiled integration-bridged chromosome rearrangements and tandem repeats of the HBV sequence within integrations. In summary, this study revealed premalignant oncogenic and sequential complex integrations and highlighted the contributions of HBV integrations to HCC development and genome instability

Biodiversity promotes ecosystem functioning despite environmental change

Three decades of research have demonstrated that biodiversity can promote the functioning of ecosystems. Yet, it is unclear whether the positive effects of biodiversity on ecosystem functioning will persist under various types of global environmental change drivers. We conducted a meta-analysis of 46 factorial experiments manipulating both species richness and the environment to test how global change drivers (i.e. warming, drought, nutrient addition or CO2 enrichment) modulated the effect of biodiversity on multiple ecosystem functions across three taxonomic groups (microbes, phytoplankton and plants). We found that biodiversity increased ecosystem functioning in both ambient and manipulated environments, but often not to the same degree. In particular, biodiversity effects on ecosystem functioning were larger in stressful environments induced by global change drivers, indicating that high-diversity communities were more resistant to environmental change. Using a subset of studies, we also found that the positive effects of biodiversity were mainly driven by interspecific complementarity and that these effects increased over time in both ambient and manipulated environments. Our findings support biodiversity conservation as a key strategy for sustainable ecosystem management in the face of global environmental change

Comparison of Different Techniques of Web GUI-based Testing with the Representative Tools Selenium and EyeSel

Context. Software testing is becoming more and more important in software development life-cycle especially for web testing. Selenium is one of the most widely used property-based Graph-User-Interface(GUI) web testing tools. Nevertheless, it also has some limitations. For instance, Selenium cannot test the web components in some specific plugins or HTML5 videos frame. But it is important for testers to verify the functionality of plugins or videos on the websites. Recently, the theory of the image recognition-based GUI testing is introduced which can locate and interact with the components to be tested on the websites by image recognition. There are only a few papers do research on comparing property-based GUI web testing and image recognition-based GUI testing. Hence, we formulated our research objectives based on this main gap. Objectives. We want to compare these two different techniques with EyeSel which is the tool represents the image recognition-based GUI testing and Selenium which is the tool represents the property-based GUI testing. We will evaluate and compare the strengths and drawbacks of these two tools by formulating specific JUnit testing scripts. Besides, we will analyze the comparative result and then evaluate if EyeSel can solve some of the limitations associated with Selenium. Therefore, we can conclude the benefits and drawbacks of property-based GUI web testing and image recognition-based GUI testing.   Methods. We conduct an experiment to develop test cases based on websites’ components both by Selenium and EyeSel. The experiment is conducted in an educational environment and we select 50 diverse websites as the subjects of the experiment. The test scripts are written in JAVA and ran by Eclipse.  The experiment data is collected for comparing and analyzing these two tools. Results. We use quantitative analysis and qualitative analysis to analyze our results. First of all, we use quantitative analysis to evaluate the effectiveness and efficiency of two GUI web testing tools. The effectiveness is measured by the number of components that can be tested by these two tools while the efficiency is measured by the measurements of test cases’ development time and execution time. The results are as follows (1) EyeSel can test more number of components in web testing than Selenium (2) Testers need more time to develop test cases by Selenium than by EyeSel (3) Selenium executes the test cases faster than EyeSel. (4) “Results (1)” indicates the effectiveness of EyeSel is better than Selenium while “Results (2)(3)” indicate the efficiency of EyeSel is better than Selenium. Secondly, we use qualitative analysis to evaluate four quality characteristics (learnability, robustness, portability, functionality) of two GUI web testing tools. The results show that portability and functionality of Selenium are better than EyeSel while the learnability of EyeSel is better than Selenium. And both of them have good robustness in web testing. Conclusions. After analyzing the results of comparison between Selenium and EyeSel, we conclude that (1) Image recognition-based GUI testing is more effectiveness than property-based GUI web testing (2) Image recognition-based GUI testing is more efficiency than property-based GUI web testing (3) The portability and functionality of property-based GUI web testing is better than Image recognition-based GUI testing (4) The learnability of image recognition-based GUI testing is better than property-based GUI web testing. (5) Both of them are good at different aspects of robustnes

Quantum Architecture Search with Meta-learning

Variational quantum algorithms (VQAs) have been successfully applied to quantum approximate optimization algorithms, variational quantum compiling and quantum machine learning models. The performances of VQAs largely depend on the architecture of parameterized quantum circuits (PQCs). Quantum architecture search (QAS) aims to automate the design of PQCs in different VQAs with classical optimization algorithms. However, current QAS algorithms do not use prior experiences and search the quantum architecture from scratch for each new task, which is inefficient and time consuming. In this paper, we propose a meta quantum architecture search (MetaQAS) algorithm, which learns good initialization heuristics of the architecture (i.e., meta-architecture), along with the meta-parameters of quantum gates from a number of training tasks such that they can adapt to new tasks with a small number of gradient updates, which leads to fast learning on new tasks. The proposed MetaQAS can be used with arbitrary gradient-based QAS algorithms. Simulation results of variational quantum compiling on three- and four-qubit circuits show that the architectures optimized by MetaQAS converge much faster than a state-of-the-art gradient-based QAS algorithm, namely DQAS. MetaQAS also achieves a better solution than DQAS after fine-tuning of gate parameters

Association of ERCC family mutations with prognosis and immune checkpoint inhibitors response in multiple cancers

Abstract The proteins encoded by the excision repair cross-complementing (ERCC) family are pivotal in DNA damage repair and maintaining genome stability. However, the precise role of the ERCC family in tumor prognosis and the effectiveness of immune checkpoint inhibitors (ICI) therapy remain uncertain. This study aimed to explore the connection between ERCC mutations and prognosis as well as the response to ICI. We observed that patients with ERCC mutations exhibited enhanced progression-free survival (PFS) and overall survival (OS) in two independent pan-cancer cohorts. Furthermore, this mutant subgroup showed higher tumor mutation burden (TMB) compared to the wild-type subgroup. Notably, ERCC mutations were associated with better OS (HR 0.54, 95% CI 0.42–0.70; P < 0.001) in pan-cancer patients who underwent ICI therapy (N = 1661). These findings were validated in a separate cohort, where patients in the ERCC mutant subgroup demonstrated improved clinical outcomes (HR 0.56, 95% CI 0.37–0.84; P = 0.03) and higher response rates (51.9% vs. 26.8%) than the wild-type subgroup. Further analysis revealed that patients with ERCC mutations displayed elevated tumor neoantigen burden (TNB) levels and increased infiltration of immune-response cells. Our study suggests that ERCC mutations are linked to enhanced immunogenicity and improved ICI efficacy, thus potentially serving as a biomarker for ICI therapy

High Power All-Fiber Supercontinuum System Based on Graded-Index Multimode Fibers

An all-fiber supercontinuum source based on graded-index multimode fibers is reported. The supercontinuum source is based on a homemade mode-locked oscillator and a three-stage picosecond amplifier, which obtained the supercontinuum by a graded-index multimode fiber. The laser output with a spectral range of 480–2440 nm, an average power of 25 W, and a repetition frequency of 8.27 MHz is obtained. To the best of our knowledge, this is the highest average power for generating a supercontinuum with an all-fiber structure based on the graded-index fiber. The effects of GRIN fiber length and different pump peak powers on the supercontinuum generation are also verified. The results showed that the graded-index multimode fiber can effectively obtain a supercontinuum with high power

Yb-Doped Fiber Chirped Pulse Amplification System Delivering 1 mJ, 231 fs at 1 kHz Repetition Rate

In this paper a single-channel chirped pulse amplification laser system based on Yb-doped photonic crystal fiber was constructed, which achieved a pulse energy output of 1 mJ with a beam quality close to the diffraction limit. Pulsed synchronous pumping was used to suppress amplified spontaneous emission at a repetition rate of 1 kHz. The de-chirped pulse width of 231 fs was achieved by precise systematic dispersion control, and the corresponding peak power reached 3.85 GW

Roles of LonP1 in Oral-Maxillofacial Developmental Defects and Tumors: A Novel Insight

Recent studies have indicated a central role for LonP1 in mitochondrial function. Its physiological functions include proteolysis, acting as a molecular chaperone, binding mitochondrial DNA, and being involved in cellular respiration, cellular metabolism, and oxidative stress. Given its vital role in energy metabolism, LonP1 has been suggested to be associated with multi-system neoplasms and developmental disorders. In this study, we investigated the roles, possible mechanisms of action, and therapeutic roles of LonP1 in oral and maxillofacial tumor development. LonP1 was highly expressed in oral-maxillofacial cancers and regulated their development through a sig-naling network. LonP1 may therefore be a promising anticancer therapy target. Mutations in LONP1 have been found to be involved in the etiology of cerebral, ocular, dental, auricular, and skeletal syndrome (CODAS). Only patients carrying specific LONP1 mutations have certain dental abnormalities (delayed eruption and abnormal morphology). LonP1 is therefore a novel factor in the development of oral and maxillofacial tumors. Greater research should therefore be conducted on the diagnosis and therapy of LonP1-related diseases to further define LonP1-associated oral phenotypes and their underlying molecular mechanisms